An expeditious route to N-glycolylneuraminic acid based on enzyme-catalyzed reaction

Atsuhito Kuboki, Hanako Okazaki, Takeshi Sugai, Hiromichi Ohta

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

A new preparative way of N-glycolylneuraminic acid (NeuGc), one of the important family of sialic acids, from N-acetylglucosamine (GlcNAc) via N-acetylmannosamine (ManNAc) was established based on the combination of chemical and enzymatic reactions. In a kinetic study of the key enzymatic reaction for this process, aldolase-catalyzed synthesis of sialic acid, an inhibitory effect of gluco-isomer on the enzymatic reaction was quantitatively clarified, and the importance of isomerically pure substrate with manno-configuration for aldolase-catalyzed reaction was suggested. A newly developed method, selective degradation of GlcNAc contaminating in the substrate by use of Rhodococcus rhodochrous IFO 15564 provided pure ManNAc to avoid such inhibitory effect of the gluco-isomer for aldolase. Starting from pure ManNAc, via mannosamine hydrochloride, acetoxyacetyl chloride was applied for introducing a protected form of glycolyl group to give N-acetylglycolylmannosamine. For the removal of acetyl protective group, a lipase from Aspergillus niger was effectively used under a mild and neutral condition to afford N-glycolylmannosamine (ManNGc), the substrate of aldolase. NeuGc was prepared in 25% yield and 7 steps from GlcNAc.

Original languageEnglish
Pages (from-to)2387-2400
Number of pages14
JournalTetrahedron
Volume53
Issue number7
DOIs
Publication statusPublished - 1997 Feb 17

Fingerprint

Fructose-Bisphosphate Aldolase
Enzymes
Isomers
Substrates
Sialic Acids
Rhodococcus
Acetylglucosamine
Aspergillus niger
Aspergillus
N-Acetylneuraminic Acid
Lipase
Chlorides
Degradation
Kinetics
N-glycolylneuraminic acid

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

An expeditious route to N-glycolylneuraminic acid based on enzyme-catalyzed reaction. / Kuboki, Atsuhito; Okazaki, Hanako; Sugai, Takeshi; Ohta, Hiromichi.

In: Tetrahedron, Vol. 53, No. 7, 17.02.1997, p. 2387-2400.

Research output: Contribution to journalArticle

Kuboki, Atsuhito ; Okazaki, Hanako ; Sugai, Takeshi ; Ohta, Hiromichi. / An expeditious route to N-glycolylneuraminic acid based on enzyme-catalyzed reaction. In: Tetrahedron. 1997 ; Vol. 53, No. 7. pp. 2387-2400.
@article{60d06659629e4ffba5394d860b893fd8,
title = "An expeditious route to N-glycolylneuraminic acid based on enzyme-catalyzed reaction",
abstract = "A new preparative way of N-glycolylneuraminic acid (NeuGc), one of the important family of sialic acids, from N-acetylglucosamine (GlcNAc) via N-acetylmannosamine (ManNAc) was established based on the combination of chemical and enzymatic reactions. In a kinetic study of the key enzymatic reaction for this process, aldolase-catalyzed synthesis of sialic acid, an inhibitory effect of gluco-isomer on the enzymatic reaction was quantitatively clarified, and the importance of isomerically pure substrate with manno-configuration for aldolase-catalyzed reaction was suggested. A newly developed method, selective degradation of GlcNAc contaminating in the substrate by use of Rhodococcus rhodochrous IFO 15564 provided pure ManNAc to avoid such inhibitory effect of the gluco-isomer for aldolase. Starting from pure ManNAc, via mannosamine hydrochloride, acetoxyacetyl chloride was applied for introducing a protected form of glycolyl group to give N-acetylglycolylmannosamine. For the removal of acetyl protective group, a lipase from Aspergillus niger was effectively used under a mild and neutral condition to afford N-glycolylmannosamine (ManNGc), the substrate of aldolase. NeuGc was prepared in 25{\%} yield and 7 steps from GlcNAc.",
author = "Atsuhito Kuboki and Hanako Okazaki and Takeshi Sugai and Hiromichi Ohta",
year = "1997",
month = "2",
day = "17",
doi = "10.1016/S0040-4020(96)01189-1",
language = "English",
volume = "53",
pages = "2387--2400",
journal = "Tetrahedron",
issn = "0040-4020",
publisher = "Elsevier Limited",
number = "7",

}

TY - JOUR

T1 - An expeditious route to N-glycolylneuraminic acid based on enzyme-catalyzed reaction

AU - Kuboki, Atsuhito

AU - Okazaki, Hanako

AU - Sugai, Takeshi

AU - Ohta, Hiromichi

PY - 1997/2/17

Y1 - 1997/2/17

N2 - A new preparative way of N-glycolylneuraminic acid (NeuGc), one of the important family of sialic acids, from N-acetylglucosamine (GlcNAc) via N-acetylmannosamine (ManNAc) was established based on the combination of chemical and enzymatic reactions. In a kinetic study of the key enzymatic reaction for this process, aldolase-catalyzed synthesis of sialic acid, an inhibitory effect of gluco-isomer on the enzymatic reaction was quantitatively clarified, and the importance of isomerically pure substrate with manno-configuration for aldolase-catalyzed reaction was suggested. A newly developed method, selective degradation of GlcNAc contaminating in the substrate by use of Rhodococcus rhodochrous IFO 15564 provided pure ManNAc to avoid such inhibitory effect of the gluco-isomer for aldolase. Starting from pure ManNAc, via mannosamine hydrochloride, acetoxyacetyl chloride was applied for introducing a protected form of glycolyl group to give N-acetylglycolylmannosamine. For the removal of acetyl protective group, a lipase from Aspergillus niger was effectively used under a mild and neutral condition to afford N-glycolylmannosamine (ManNGc), the substrate of aldolase. NeuGc was prepared in 25% yield and 7 steps from GlcNAc.

AB - A new preparative way of N-glycolylneuraminic acid (NeuGc), one of the important family of sialic acids, from N-acetylglucosamine (GlcNAc) via N-acetylmannosamine (ManNAc) was established based on the combination of chemical and enzymatic reactions. In a kinetic study of the key enzymatic reaction for this process, aldolase-catalyzed synthesis of sialic acid, an inhibitory effect of gluco-isomer on the enzymatic reaction was quantitatively clarified, and the importance of isomerically pure substrate with manno-configuration for aldolase-catalyzed reaction was suggested. A newly developed method, selective degradation of GlcNAc contaminating in the substrate by use of Rhodococcus rhodochrous IFO 15564 provided pure ManNAc to avoid such inhibitory effect of the gluco-isomer for aldolase. Starting from pure ManNAc, via mannosamine hydrochloride, acetoxyacetyl chloride was applied for introducing a protected form of glycolyl group to give N-acetylglycolylmannosamine. For the removal of acetyl protective group, a lipase from Aspergillus niger was effectively used under a mild and neutral condition to afford N-glycolylmannosamine (ManNGc), the substrate of aldolase. NeuGc was prepared in 25% yield and 7 steps from GlcNAc.

UR - http://www.scopus.com/inward/record.url?scp=0031575587&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031575587&partnerID=8YFLogxK

U2 - 10.1016/S0040-4020(96)01189-1

DO - 10.1016/S0040-4020(96)01189-1

M3 - Article

VL - 53

SP - 2387

EP - 2400

JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 7

ER -